[Experimental use of liposomes carrying an antimetabolite (mitoxantrone) in filtering surgery]

Fibroblast proliferation plays a prominent role in closure of conjunctival filtering blebs and extensive investigations are being carried out to optimize antiproliferative pharmacotherapy in the prevention of filtering bleb failure in glaucomatous eyes with a poor prognosis undergoing surgery. Intercalating agents such as doxorubicin or daunorubicin have been shown to decrease fibroblast proliferation in tissue cultures. A liposomal delivery system was developed in an attempt to obtain a sustained release effect and to minimize ocular side effects of mitoxantrone (Novantrone, MITX), an antineoplastic agent with intercalating properties. The objectives of this study were to demonstrate the entrapment stability of MITX in multilamellar vesicles (reaching about 60% and remaining at this level for 8-weeks storage) and to investigate its activity in vitro (cell cultures) and in vivo (sclerectomy ab externo in rabbits). We showed that entrapped MITX inhibited in a dose-dependent manner subconjunctival fibroblast proliferation (ID50: 0.03 micrograms/l at D3 in cultures) and prolonged the success of filtration surgery in rabbits (decrease of intraocular pressure of 8 mm Hg in treated eyes versus 1.8 mm Hg in control eyes; p < 0.01). These results indicate the potential of MITX-entrapped liposomes in the control of conjunctival scarring in filtering bleb surgery.